An ancient defense system eliminates unfit cells from developing tissues during cell competition

Developing tissues that contain mutant or compromised cells present risks to animal health. Accordingly, the appearance of a population of suboptimal cells in a tissue elicits cellular interactions that prevent their contribution to the adult. Here we report that this quality control process, cell competition, uses specific components of the evolutionarily ancient and conserved innate immune system to eliminate Drosophila cells perceived as unfit. We find that Toll-related receptors (TRRs) and the cytokine Spatzle (Spz) lead to NF kappa B-dependent apoptosis. Diverse loser cells require different TRRs and NF kappa B factors and activate distinct pro-death genes, implying that the particular response is stipulated by the competitive context. Our findings demonstrate a functional repurposing of components of TRRs and NF kappa B signaling modules in the surveillance of cell fitness during development.